1. Field of the Invention
This invention relates to compositions which promote repair of tissue, particularly fibroblast cells, in animals, particularly human beings. This invention further relates to a method of treating wounds by the topical or systemic administration of the compositions.
2. Description of the Prior Art
There is a continuing need for the promotion of rapid cell proliferation at the site of wounds, burns, diabetic and decubitus ulcers, and other traumata.
A number of "growth factors" are known, which promote the rapid growth of animal cells. These growth factors include epidermal growth factor (EGF), transforming growth factors (TGF's), and nerve growth factors (NGF). However, prior to this invention, none of these growth factors have been found to be pharmaceutically acceptable agents for the acceleration of wound healing.
It has been shown that the mitogenic activity of insulin (a hormone) can be increased many-fold by the presence of prostaglandin F.sub..alpha. (not exactly a hormone, but having similar properties--it causes constriction of vascular smooth muscle), see L. Jimenez de Asua et al, Cold Spring Harbor Conf. Cell Proliferation, Vol. 6, Sato, ed., Cold Spring Harbor Labs., New York (1979) at pp. 403-424. Similar activation of insulin has been reported with fibroblast growth factor by P. S. Rudland et al, Proc. Natl. Acad. Sci. USA, 71, 2600-2604 (1974) and with EGF by R. W. Holley et al, Proc. Natl. Acad. Sci. USA, 71, 2908-2911 (1974). Furthermore, in the "competence-progression" scheme of C. D. Stiles et al, in Proc. Natl. Acad. Sci. USA, 76: 1279-1283 (1979), positive effects on cell growth have been demonstrated for platelet-derived growth factor or fibroblast growth factor in combination with members of the insulin family such as somatomedins A and C, the insulin-like growth factors.
Many new peptide growth factors have been isolated and characterized recently, as indicated in Tissue Growth Factors, R. Baserga, ed., Springer-Verlag pub., New York (1981), however there have been few studies on the activity of these materials in vivo. In many cases, the relatively small amounts of peptides available have limited the ability to study their properties in vivo. An important area for potential application of peptide growth factors is the enhancement of wound healing. Despite the need for rapid wound healing in the treatment of severe burns, trauma, diabetic and decubitus ulcers, and many other conditions, at present there is no practical way to accelerate wound healing with pharmacological agents. Although it is suggested in Tissue Growth Factors, supra, at p. 123 that EGF might be of benefit in this area, it has yet to be extensively used in a practical way for wound healing.